Lack of association between flow-mediated endothelium-dependent vasodilatation and biomarkers of endothelial dysfunction in patients with severe rheumatoid arthritis

Abstract

Accelerated atherogenesis is one of the main reasons for the increased mortality observed in patients with rheumatoid arthritis (RA) [1]. Progressive impairment of macrovascular and microvascular endothelium-dependent vasodilatation is associated with increased risk of cardiovascular complications. Endothelial function can be noninvasively assessed by postocclusive reactive hyperemia, either as increase in the brachial artery blood flow, as flowmediated vasodilatation of the afferent artery (macrovascular), or as increase in skin microcirculatory flow detected by laser Doppler. Both macrovascular and microvascular studies have confirmed the presence of endothelial dysfunction in patients with long-standing RA [2, 3]. Elevated circulating levels of soluble adhesion molecules are also associated with cardiovascular risk factors and predict atherosclerosis and CV events [4, 5]. Measurement of these biomarkers of endothelial activation and dysfunction has confirmed the presence of endothelial dysfunction in patients with RA [6]. Since administration of anti-TNF-a resulted in a rapid improvement in endothelial function in patients with this chronic inflammatory disease [7], and reduction in some biomarkers of endothelial dysfunction was also observed in these patients following anti-TNF-a drugs [8], an issue of potential interest may be to establish whether a correlation between the levels of soluble biomarkers of endothelial dysfunction and the presence of impairment of endothelium-dependent vasodilatation exists in patients with RA. In this regard, Meyer et al. [9] assessed whether microvascular changes in capillary blood cell velocity had correlation with levels of soluble adhesion molecules in 30 patients with RA. However, no correlation between capillary blood cell velocity and serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) was found. To further investigate into this issue, we aimed to determine whether levels of serum biomarkers of endothelial dysfunction might correlate with values of macrovascular flowmediated endothelium-dependent vasodilatation in 14 patients with severe RA refractory to conventional diseasemodifying anti-rheumatic drugs. Ethical approval and informed consent were obtained. All patients had severe disease (DAS28 in all cases greater than 3.2), refractory to conventional disease-modifying anti-rheumatic drugs including methotrexate, and were receiving periodical treatment with infliximab therapy. Evaluation of brachial M. A. Gonzalez-Gay (&) Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IFIMAV, Avenida de Valdecilla s/n, 39008 Santander, Spain e-mail: miguelaggay@hotmail.com